N-terminal Fragment Of pro-B-type Natriuretic Peptide Research Articles

Prediction of Acute Myocardial Injury in Noncardiac Surgery in Patients at Risk for Major Adverse Cardiovascular and Cerebrovascular Events: A Multivariable Risk Model.

The best use of perioperative cardiac biomarkers assessment is still under discussion. Massive postoperative troponin surveillance can result in untenably high workloads and costs for health care systems and potentially harmful interventions for patients. In a cohort of patients at risk for major adverse cardiovascular and cerebrovascular events (MACCEs), we aimed to (1) determine whether preoperative biomarkers can identify patients at major risk for acute myocardial injury in noncardiac surgery, (2) develop a risk model for acute myocardial injury prediction, and (3) propose an algorithm to optimize postoperative troponin surveillance. Prospective, single-center cohort study enrolling consecutive adult patients (≥45 years) at risk for MACCE scheduled for intermediate-to-high-risk noncardiac surgery. Baseline high-sensitivity troponin T (hsTnT) and N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), as well as hsTnT on the first 3 postoperative days were obtained. The main outcome was the occurrence of acute myocardial injury. Candidate predictors of acute myocardial injury were baseline concentrations of hsTnT ≥14 ng/L and NT-proBNP ≥300 pg/mL and preoperative and intraoperative variables. A multivariable risk model and a decision curve were constructed. Of 732 patients, 42.1% had elevated hsTnT and 37.3% had elevated NT-proBNP levels at baseline. Acute myocardial injury occurred in 161 patients (22%). Elevated baseline hsTnT, found in 84% of patients with acute myocardial injury, was strongly associated with this outcome: odds ratio (OR), 12.08 (95% confidence interval [CI], 7.78-19.42). Logistic regression identified 6 other independent predictors for acute myocardial injury: age, sex, estimated glomerular filtration rate (eGFR) <45 mL·min -1 ·1.73 m -2 , functional capacity <4 METs or unknown, NT-proBNP ≥300 pg/mL, and estimated intraoperative blood loss. The c -statistic for the risk model was 77% (95% CI, 0.73-0.81). The net benefit of the model began at a risk threshold of 7%. Baseline determination of cardiac biomarkers in patients at risk for MACCE shortly before intermediate- or high-risk noncardiac surgery helps identify those with the highest risk for acute myocardial injury. A baseline hsTnT ≥14 ng/L indicates the need for postoperative troponin surveillance. In patients with baseline hsTnT <14 ng/L, our 6-predictor model will identify additional patients at risk for acute myocardial injury who may also benefit from postoperative surveillance.

A new composite indicator consisting of left ventricular extracellular volume, N-terminal fragment of B-type natriuretic peptide, and left ventricular end-diastolic volume is useful for predicting reverse remodeling after catheter ablation for atrial fibrillation.

Recently, myocardial extracellular volume (ECV) analysis has been measurable on computed tomography (CT) using new software. We evaluated the use of cardiac CT to estimate the myocardial ECV of left ventricular (LV) myocardium (LVM) to predict reverse remodeling (RR) in cases of atrial fibrillation (AF) after catheter ablation (CA). Four hundred and seven patients underwent CA for AF in our institution from April 2014 to Feb 2021. Of these, 33 patients (8%) with an LVEF ≤ 50% and who had undergone CT were included in our study. We estimated the LVM ECV using commercial software to analyze the CT data. RR was defined as an improvement in LVEF to > 50% after CA. LVEF increased to > 50% in 24 patients (73%) after CA. In all 24 patients, LVM ECV, LV end-diastolic and end-systolic volumes (LVEDV and LVESV), and the n-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) were significantly lower than in the other nine patients (P = 0.0037, 0.0273, 0.0443, and < 0.0001). On receiver operating characteristic curve analysis, the best cut-off of ECV, LVEDV, LVESV and NT-proBNP for the prediction of RR were 37.73%, 120mL, 82mL, and 1267pg/mL, respectively. We newly defined the ENL (ECV, NT-proBNP, and LVEDV) score as the summed score for the presence or absence (1 or 0; maximum score = 3) of ECV, NT-proBNP, and LVEDV values less than or equal to each best cut-off value, and found that this score gave the highest area under the curve for the prediction of RR (0.9583, P < 0.0001). The ENL score may be useful for predicting RR in patients with AF undergoing CA.

Diagnostic utility of total NT-proBNP testing by immunoassay based on antibodies targeting glycosylation-free regions of NT-proBNP.

The N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a widely used heart failure (HF) biomarker. Commercial NT-proBNP immunoassays detect only a subfraction of endogenous NT-proBNP, as the antibodies target a region of NT-proBNP that could be glycosylated at Ser44. The diagnostic utility of immunoassays measuring total NT-proBNP remains unclear. NT-proBNP was measured in 183 HF and 200 non-HF patients diagnosed by two independent cardiologists blinded to NT-proBNP results. Plasma samples either non-treated or treated with a mixture of glycosidases were analyzed by the Elecsys proBNP II assay (Roche Diagnostics, based on antibodies targeting a glycosylated region of NT-proBNP) and the SuperFlex NT-proBNP assay (PerkinElmer, based on antibodies targeting regions of NT-proBNP that are free of O-glycans). The diagnostic accuracy of the two assays was analyzed by comparison of ROC curves. The ROC-AUC for the proBNP II assay was 0.943(95% CI 0.922-0.964) for NT-proBNP measured in untreated samples and 0.935 (0.913-0.958) for NT-proBNP measured in glycosidase-treated samples. The SuperFlex NT-proBNP assay in untreated samples gave a ROC-AUC of 0.930 (95% CI 0.907-0.954). The median percentage of non-glycosylated NT-proBNP to total NT-proBNP was 1.5-1.6-fold lower in the non-HF group compared to that in the HF group. The clinical value of total NT-proBNP for HF diagnosis was similar to the subfraction of NT-proBNP that was non-glycosylated at Ser44. The lower percentage of non-glycosylated NT-proBNP to total NT-proBNP in non-HF patients suggests that total NT-proBNP might be more sensitive in individuals without current or prior symptoms of HF.

Age-Stratified Cut-Off Values for Serum Levels of N-Terminal ProB-Type Natriuretic Peptide and Mortality from Sepsis in Children Under Age 18 Years: A Retrospective Study from a Single Center

BackgroundThe N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) is an established predictive marker for sepsis-related mortality in adult. This retrospective study aimed to determine age-stratified cut-off values for serum levels of NT-proBNP and mortality from sepsis in children under 18 years.Material/MethodsPatients were stratified by age as follows: <1 year, 1–3 years, 4–6 years, and 7–18 years (age groups). The control group consisted of age- and sex-matched healthy children. Serum NT-proBNP levels were detected by laboratory assays in the participants. The appropriate serum NT-proBNP cut-off values for predicting short-term mortality of the sepsis patients were calculated via receiver operating characteristic (ROC) curve analyses.ResultsAmong 327 pediatric patients with sepsis, the serum NT-proBNP cut-off concentrations for predicting sepsis-related mortality in the <1 year, 1–3 years, 4–6 years, and 7–18 years age groups were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively (P<0.001). The area under the ROC curve (AUC) values for these were 0.815, 0.812, 0.806 and 0.725, respectively (P<0.001).ConclusionsThis retrospective study provided the age range-specific serum NT-proBNP cut-off concentrations for predicting short-term mortality in children. In children <1 year, 1–3 years, 4–6 years, and 7–18 years, age-stratified cut-off values that predicted sepsis-associated mortality were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively.

Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery.

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

Left Ventricular Strain: A Reliable Predictor of Short-Term Outcomes in Patients with Anterior Wall Myocardial Infarction without Heart Failure.

Background:Left ventricular ejection fraction (LVEF) is a key determinant in decision-making after acute myocardial infarction (MI). Little is known of its relationship with left ventricular Strain and N-Terminal fragment of pro-B-type Natriuretic Peptide (NT-pro-BNP) following acute anterior wall MI (AWMI).Materials and Methods:We conducted a prospective cohort study of patients with a diagnosis of acute AWMI and the absence of overt heart failure (HF). Assessment of LVEF, strain parameters on echocardiography was done, and NT-pro-BNP levels were obtained. Follow-up for adverse cardiac events was done for 30 days postdischarge. Correlation of LVEF and NT-pro-BNP with various strain parameters were ascertained.Results:Of the total of 50 patients of AWMI enrolled, the mean LVEF in the study was 43.46 ± 3.72%.Eleven patients (22%) had adverse events at 30 days of follow-up. Patients with adverse events had significantly higher overall peak systolic longitudinal strain (PSLS), lower mid-region peak systolic longitudinal velocity (PSLV), and basal region PSLV. A significant negative correlation was observed between LVEF and mean Peak PSLS of combined apical plus mid regions of the left ventricle (r = −0.700). Log10-NT-pro BNP also showed a strong negative correlation with overall PSLV (r = −0.792) as well as regional PSLV values of combined apical plus mid (r = −0.763) and basal segments (r = −0.748).Conclusions:In patients with AWMI without HF, PSLS and PSLV are good predictors of adverse outcomes at 30-day follow-up. Furthermore, NT-pro BNP can also be an indirect predictor of strain parameters on echocardiography.

Preoperative myocardial troponin T elevation is associated with the fracture type in patients with proximal femoral fracture.

Cardiovascular complications are common in hip fracture patients but the role of fracture type and operative method in these is unclear. This prospective cohort study aimed to evaluate the impact of fracture- and operative characteristics on perioperative cardiovascular complications and prognosis in unselected hip fracture patients. During a 7-month trial registration period, a population of 197 consecutive hip fracture patients (median age 84 years) diagnosed with femoral neck or pertrochanteric fracture was formed. The exclusion criteria were patient refusal, subtrochanteric fracture, or death preoperatively. Pre- and postoperative troponin T (TnT) elevation, perioperative N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) level, perioperative cardiovascular adverse events, and all-cause 30-day and 2- and 5-year mortalities were studied. Femoral neck fracture was independently associated with preoperative myocardial injury witnessed by TnT elevation (HR 2.95, 95% confidence interval 1.21-7.19, p = 0.018). The fracture type, surgery delay, or operative method were not significantly associated with NT-proBNP levels, cardiovascular adverse event diagnoses, or prognosis. Cardiovascular adverse events were clinically diagnosed in 28 (14%) participants, and these had a higher mortality compared to participants without such diagnosis (at 30 days, 32% vs 5%; 2 years, 71% vs 31%; and 5 years, 86% vs 59%; p < 0.001). While the femoral neck fracture independently predicts preoperative cardiovascular morbidity, the operative method does not affect perioperative cardiovascular complications or the prognosis, and it may be selected by the treating clinician based on other criteria.

Usefulness of Serum Cardiac Biomarkers for Predicting In-Hospital Cardiac Complications in Acute Hip Fracture: A Prospective Cohort in 20 High Surgical Risk patients with Age over 55 Years.

Background. Serum cardiac biomarkers have recently been demonstrated to be useful for predicting perioperative complication after hip fracture (HF). However, no previous study has revealed the comparative efficacy of different cardiac biomarkers in high surgical risk HF patients. Methods. A prospective study was conducted, from June to December 2016, in 20 acute HF patients with American Society of Anesthesiologists (ASA) grade 3 or 4. All patients received blood test for high sensitivity Troponin-I (hsTnI) and N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) at the time of admission and 24 hours postoperatively. Perioperative data and in-hospital, 3-month, and 6-month postoperative complications were collected. The complications were classified as cardiac and noncardiac HF-related complications. Results. The average patients' age was 79±8 years. Six patients (30%) were male. The incidence of PCI was 30% (n=6). None of the patients (0%) died during the 6-month postoperative followup period. In-hospital overall cardiac and noncardiac complications were found in 12(60%), 5(30%), and 7(45%), respectively. The mean serum hsTnI levels in the patients with cardiac complication were significantly greater than those in the patients without cardiac complication at both time of admission (99.5 ng/mL vs 5.5 ng/mL, p=0.006) and 24 hours postoperatively (28.6 ng/mL vs 9.4 ng/mL, p=0.013). The mean serum NT-proBNP levels in patients with cardiac complication were also greater but nonsignificantly compared to those in the patients without cardiac complication at both time of admission (2299 pg/mL vs 281 pg/mL, p=0.239) and 24 hours postoperatively (2266 pg/mL vs 586 pg/mL, p=0.061). The other significant preoperative predictors for cardiac complication were low hemoglobin level (p=0.014), low glomerular filtration rate level (p=0.039), and ASA grade 4 (p=0.005). Conclusion. In-hospital cardiac complication in high-risk HF patients was significantly associated with the abnormal rise of serum hsTnI level. Therefore, we recommended using the hsTnI test in the perioperative evaluation in high-risk HF patients. Trial registration number is TCTR20160711002.

Relationship of N-Terminal fragment of Pro-B-Type Natriuretic Peptide and copeptin with erythrocytes-related parameters: A population-based study

BackgroundPlasma levels of natriuretic peptides (NP) have been inversely related to hemoglobin (Hb) concentration in prior studies. However, the mechanism underlying this association remains unclear. We aimed to obtain further insights into potential mechanisms for this correlation in a cohort of healthy adults. MethodsA population-based study was performed among 2113 healthy adults aged 25–41years. Relationships of N-Terminal fragment of Pro-B-Type Natriuretic Peptide (NT-proBNP) or copeptin with volume-dependent (Hb, hematocrit (Hct), erythrocyte count (EC), mean corpuscular Hb concentration (MCHC)) and volume-independent (mean corpuscular volume (MCV), mean corpuscular Hb (MCH)) erythrocyte-related parameters were assessed using sex-specific multivariable linear regression analyses. ResultsThe median age was 36.7years. Median NT-proBNP (ng/L) levels were 49.5 and 20 among women and men, respectively (p<0.0001). Mean (standard deviation) Hb (g/L) levels were 130.1(9.1) and 149.7(8.6) among women and men, respectively (p<0.0001). Among men, multivariable adjusted β-coefficients (95% confidence interval) for NT-proBNP were −1.68 (−2.36; −1.01), p<0.0001 for Hb; −0.38 (−0.57; −0.20), p<0.0001 for Hct; −0.06 (−0.09; −0.04), p<0.0001 for EC; −0.78 (−1.50; −0.07), p=0.03 for MCHC; 0.26 (−0.04; 0.56), p=0.09 for MCV; and 0.03 (−0.08; 0.14), p=0.61 for MCH. For copeptin, these relationships were 1.36 (0.39; 2.32), p=0.006; 0.41 (0.15; 0.68), p=0.002; 0.06 (0.02; 0.09), p=0.002; −0.17 (−1.19; 0.86), p=0.75; −0.12 (−0.55; 0.31), p=0.58 and −0.05 (−0.21; 0.10), p=0.52. Similar results were observed among women. ConclusionsWe found significant relationships of NT-proBNP and copeptin with volume-dependent but not volume-independent erythrocyte-related parameters, suggesting that hemodilution may at least in part explain these associations.

Determining the Optimal Cutoff Values of Plasma N-Terminal Pro–B-Type Natriuretic Peptide Levels for the Diagnosis of Heart Failure in Children of Age up to 14 Years

BackgroundPlasma N-terminal fragment of pro–B-type natriuretic peptide (NT-proBNP) is a biomarker of heart failure (HF). However, the optimal cutoff value of plasma NT-proBNP for the diagnosis of HF in children is unknown. The objective of this study was to determine the appropriate cutoff value of plasma NT-proBNP for the diagnosis of HF in children ≤14 years old. Methods and ResultsPlasma NT-proBNP concentrations were detected in pediatric HF patients using standard clinical assays. Patients were stratified into 4 groups by age: 0–1 year, 1–3 years, 4–7 years, and 8–14 years. Case-matched healthy children were recruited as control subjects. HF was diagnosed with the use of the modified Ross score. The optimal cutoff value of plasma NT-proBNP for the diagnosis of HF was determined by analyzing receiver operating characteristic (ROC) curves and the resulting sensitivity, specificity, and Youden index (J). In healthy children, plasma NT-proBNP level and age were negatively correlated (r = −0.739; P < .001). In HF patients aged 0–1 year, 1–3 years, 4–7 years, and 8–14 years, respectively, areas under the ROC curves were 0.795, 0.786, 0.783, and 0.696; 95% confidence intervals were 0.689–0.901, 0.669–0.903, 0.662–0.904, and 0.487–0.905; and J values were 0.715, 0.708, 0.706, and 0.679. Optimal cutoff values of plasma NT-proBNP for the diagnosis of HF were 502 ng/L, 456 ng/L, 445 ng/L, and.355 ng/L. ConclusionsAge-stratified analysis of plasma NT-proBNP levels in children provides new parameters for diagnosing HF.

Metformin treatment may be associated with decreased levels of NT-proBNP in patients with type 2 diabetes

Individuals with type 2 diabetes (T2DM) are at increased risk of cardiovascular disease, including heart failure (HF). In patients with T2DM elevated serum concentrations of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) correlate with cardiovascular morbidity and mortality. We aimed to identify predictors of increased serum NT-proBNP levels in patients with T2DM. The study included 185 patients with T2DM treated with either oral antidiabetic agents (49.7%) or insulin (17.8%), or both (32.5%). We divided the patients into two groups: with high (>200 pg/mL) and low (≤200 pg/mL) NT-proBNP concentrations. We found differences between the patients with high and low NT-proBNP levels including age, prevalence of dyslipidemia and HF, history of previous myocardial infarction (MI), heart rate, hemoglobin level, platelet count, creatinine, urea and uric acid concentrations, use of beta-blockers, loop diuretics, metformin and insulin. In a multivariate analysis metformin was a negative predictor of increased NT-proBNP concentration. Age, history of HF and decreased estimated glomerular filtration rate (eGFR) were positive predictors. We found no correlation between NT-proBNP serum concentration and insulin treatment or history of coronary artery disease or MI. Metformin correlates with lower concentrations of NT-proBNP in patients with T2DM.

Parallel evolution of circulating FABP4 and NT-proBNP in heart failure patients

BackgroundCirculating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF).MethodsWe included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons.ResultsIn the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF.ConclusionsFABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.

N-terminal fragment of pro-B-type natriuretic peptide is a predictor of cardiac events in high-risk patients undergoing acute hip fracture surgery

The aim of this investigation was to assess the incidence of elevated N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and its relation to outcome defined as perioperative adverse cardiac events and all-cause mortality in high-risk patients undergoing non-elective surgery for hip fracture. A cohort of patients with hip fractures were extracted from a prospective observational study of high-risk patients (ASA class III or IV) undergoing emergency surgery. NT-proBNP and troponin I were measured before operation. An NT-proBNP > or = 3984 ng litre(-1) was set as the cut-off level for significance. Perioperative adverse cardiac events and 30 day and 3 month mortality were recorded. Sixty-nine subjects were included. Thirty-four subjects (49%) had an NT-proBNP > or = 3984 ng litre(-1) before surgery. Thirty-four subjects (49%) had a perioperative adverse cardiac event. Of these, 22 subjects (65%) had NT-proBNP above the diagnostic threshold compared with 12 subjects (34%) who had an NT-proBNP below the diagnostic threshold (P=0.01). Preoperative NT-proBNP > or = 3984 ng litre(-1) [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.0-8.9] and congestive heart failure (OR 3.0; 95% CI 1.0-9.0) were independent predictors of perioperative adverse cardiac events. A total of eight subjects (12%) died within 30 days after operation. There is a high incidence of elevated NT-proBNP in subjects undergoing non-elective hip fracture surgery. Preoperative NT-proBNP is a valuable predictor of cardiac complications in the perioperative period.

Clinical applications of N-terminal pro B-type natriuretic peptide in heart failure and other cardiovascular diseases

N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) has emerged as an important adjunct in the management of heart failure (HF) and other cardiovascular diseases. NT-proBNP is a 76-amino acid peptide created during cleavage of the precursor molecule, Pro B-type natriuretic peptide (ProBNP). NT-proBNP is of significant diagnostic value in patients presenting with possible HF and is an important prognostic factor in this condition and other cardiovascular diseases. Ongoing research supports the potential value of this biomarker in non-cardiovascular disease. This review will describe clinical applications of NT-proBNP in HF and a broad range of other conditions.

A glycosylated form of the human cardiac hormone pro B-type natriuretic peptide is an intrinsically unstructured monomeric protein

The N-terminal fragment of pro B-type natriuretic peptide (NT-proBNP) and proBNP are used as gold standard clinical markers of myocardial dysfunction such as cardiac hypertrophy and left ventricle heart failure. The actual circulating molecular forms of these peptides have been the subject of intense investigation particularly since these analytes are measured in clinical assays. Conflicting data has been reported and no firm consensus on the exact nature of the molecular species exists. Because these clinical assays are immunoassay-based, specific epitopes are detected. It is conceivable then that certain epitopes may be masked and therefore unavailable for antibody binding, thus the importance of determining the nature of the circulating molecular forms of these analytes. This situation is an unavoidable Achilles’ heel of immunoassays in general. A recombinant O-linked glycosylated form of proBNP has been show to mimic some of the properties of extracted plasma from a heart failure patient. In particular the recombinant and native material co-migrated as diffuse Western-immunostained bands on SDS–PAGE and each band collapsed to an apparent homogeneous band following deglycosylation. Thus, glycosylated-proBNP may be one such circulating form. Here we provide extensive physiochemical characterization for this O-linked protein and compare these results to other described circulating species, non-glycosylated-proBNP and NT-proBNP. It will be shown that glycosylation has no influence on the secondary and quaternary structure of proBNP. In fact, at moderate concentration in benign physiological neutral pH buffer, all three likely circulating species are essentially devoid of major secondary structure, i.e., are intrinsically unstructured proteins (IUPs). Furthermore, all three proteins exist as monomers in solution. These results may have important implications in the design of NT-proBNP/BNP immunoassays.

N-Terminal Pro-B-Type Natriuretic Peptide as an Indicator of Possible Cardiovascular Disease in Severely Obese Individuals: Comparison with Patients in Different Stages of Heart Failure

Mild stages of heart failure might be difficult to diagnose in severely obese individuals with a body mass index (BMI) >40 kg/m(2). Measurement of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is feasible for detecting cardiac impairment. The aims of our study were to measure NT-proBNP in plasma of severely obese patients and to compare the results with results for patients in different stages of manifest cardiac dysfunction. In 61 severely obese individuals (median BMI, 43.2 kg/m(2)) and 96 nonobese patients with existing heart failure [classified into New York Heart Association (NYHA) classes I-IV], NT-proBNP was measured in the fasting condition. A medical history, physical examination, electrocardiography, blood chemistry, and chest x-ray were performed in the obese group. In addition, echocardiography was performed in the NYHA group. In obese individuals, NT-proBNP was increased to a median of 356 (interquartile range, 221-458) pmol/L [854 (530-1099) ng/L] and was comparable (P >0.05) to the median value for NYHA I patients {289 (258-451) pmol/L [694 (619-1082) ng/L]}, but was significantly lower than in the other NYHA groups (P <0.001 for each). The prognostic relevance of increased NT-proBNP for risk of developing cardiac insufficiency in severely obese patients needs to be further evaluated.